Effect of phosphorylation of protamine-like cationic peptide on the binding affinity to DNA

Protamines are more arginine-rich and more basic than histones and are responsible for providing a highly com-pacted shape to the sperm heads in the testis. Phosphorylation and dephosphorylation are two events that occur in the late phase of spermatogenesis before the maturation of sperms. In this work, we have studied the effect of phosphorylation of prot-amine-like cationic peptides using all-atom molecular dynamics simulations. Through thermodynamic analyses, we found that phosphorylation reduces the binding efficiency of such cationic peptides on DNA duplexes. Peptide phosphorylation leads to a less efficient DNA condensation, due to a competition between DNA-peptide and peptide-peptide interactions. We hypothesize that the decrease of peptide bonds between DNA together with peptide self-assembly might allow an optimal re-organization of chromatin and an efficient condensation through subsequent peptide dephosphorylation. Based on the globular and compact conformations of phosphorylated peptides mediated by arginine-phosphoserine H-bonding, we furthermore postulate that phosphorylated protamines could more easily intrude into chromatin and participate to histone release through disruption of histone-histone and histone-DNA binding during spermatogenesis.

Automated summary

Phosphorylation of protamine-like cationic peptides reduces their binding efficiency with DNA duplexes, leading to less efficient DNA condensation. Phosphorylated protamines are speculated to easily intrude into chromatin and disrupt histone-histone and histone-DNA binding during spermatogenesis.